Immune-defective mice and a perinatal surgical rodent model developed in our laboratories, both of which exhibit abnormal learning behaviors, show developmental brain anomalies that are similar to those seen in dyslexics. In the first period of the Program Project, we documented brain, behavioral and immunological abnormalities in an animal model. We carried out preliminary research that suggested a special role of the uterine environment for some immunological and behavioral characteristics. During the second period, we characterized further cellular, connectional, behavioral (including early life experience), and developmental characteristics of the anomalies, as well as genetic influences on their origin and effects of pharmacological manipulations. We also demonstrated the lack of substantial interaction among malformations, immunological parameters, and intrauterine environment. Related research in humans and animals demonstrated that the distinction between defects in low-level sensory processing and those in higher-level cognition is pivotal in determining the pathogenesis of dyslexia. The purpose of the continuation of this program project is to pursue lines of evidence that have been productive and convergent between our line of research and that of our colleagues. Four research projects and 4 core functions will comprise the Program Project. Two anatomy projects will look at the developmental anatomical consequences of minor cortical malformations, either spontaneous or induced, on connectionally related cortical and subcortical regions, in an attempt to explain functional abnormalities at both high and low levels of processing. Amelioration of anatomic effects will be attempted through environmental enrichment. A neurophysiology project will examine the synaptic characteristics of these connections, which are likely to be part of the mechanism by which cross-level developmental influences act. A neurobehavioral project will investigate behaviors at multiple levels of processing and the effects of early environmental manipulation. The 2 anatomical cores will support these projects and an especially designed neuroimaging core will be instituted to allow for longitudinal research in living animals and to optimize methods for best demonstrating minor cortical malformations in vivo . A data processing Core will serve all projects.